PROJECT SUMMARY Adverse local tissue reactions (ALTRs) associated with metal particulate debris and/or ions released from modular junctions and other metal interfaces (e.g. prosthesis/bone) are the result of immune responses which have presented as granulomas, necrotic tissue, pseudotumors, etc. Although wear and corrosion (?tribocorrosion?) have long been recognized as the problems endangering the long term survival of orthopedic implants, much remains unknown about the interaction of host tissue with degradation products. We hypothesize that metal degradation products resulting from tribocorrosion are dynamically bioreactive (i.e. time-dependent), where implant debris is initially highly bioreactive and then decreases over time as it becomes more electrochemically stable. Once validated in this study, our development of a ?Tribocorrosion Bioreactor? will allow direct mechanistic investigations between degradation products and cells, and will enable preclinical testing of meta-stable tribocorrosion products that are generated in situ. Here, we will evaluate if real time metal tribocorrosion products are excessively reactive aseptic stimuli eliciting both innate (macrophage) and adaptive (lymphocyte) immuno-reactivity and, thus, differ from more time-stabilized complexes formed from the same debris. Demonstrating the phenomenon of time-dependent implant debris reactivity is critical to understanding the clinical impact of freshly produced metal implant debris from both wear and corrosion. It will provide a significant leap forward into the next generation of in vitro testing of orthopedic materials.